Field of the Invention
The present invention relates to methods for treating premature ejaculation and methods for controlling a premature ejaculation treatment device.
Discussion of the Background
Ejaculatory dysfunction is a class of male sexual disorders, which includes premature or rapid ejaculation, delayed ejaculation, complete inability to ejaculate, retrograde ejaculation, painful ejaculation, and the like. Among them, premature ejaculation is the most common ejaculatory dysfunction, and reportedly affects 5-40% of sexually active men (Nature Clinical Practice Urology, 5: 93-103, 2008). Premature ejaculation is a male sexual disorder characterized by ejaculation that always or nearly always occurs prior to or within about 1 min of vaginal penetration from the first sexual experience (life-long premature ejaculation), a clinically significant reduction in intravaginal ejaculatory latency time (IELT), often to about 3 minutes or less, during sexual intercourse (acquired premature ejaculation), the inability to delay ejaculation in all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy (Journal of Sexual Medicine, 11: 1392-1422, 2014).
As treatment options for premature ejaculation, pharmacologic, psychological, and behavioral therapies are known. As pharmacological agents for treating premature ejaculation, topical anesthetic agents directly applied to the glans of the penis and oral agents such as tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) have been used (Journal of Sexual Medicine, 3: Suppl 4, 309-317, 2006; Journal of Sexual Medicine, 11: 1392-1422, 2014).
However, the topical anesthetic agents directly applied to the glans of the penis cause penile hypoesthesia, transvaginal contamination, and female genital anesthesia. Further, the anesthetic agents must be applied to the penis right before sexual intercourse, making such agents less convenient.
The oral agents may cause systemic adverse effects such as nausea, diarrhea, insomnia, and the like, while the antidepressants bring about concerns over change in mental condition. Further, there is concern that SSRIs may be associated with spermatogenesis hypofunction (F1000Prime reports, 6: 55, 2014).
It has been reported that behavioral and psychological therapies may work only for a short period of time with low efficiency (Nature Clinical Practice Urology, 5: 93-103, 2008; F1000Prime Reports, 6: 55, 2014).
There are several reports suggesting that patients with premature ejaculation have penile hypersensitivity (The Journal of Urology, 156: 979-981, 1996; The Journal of Urology, 158: 451-455, 1997; Urology, 11: 81-82, 1978). Further, there is a report indicating that the number of dorsal penile nerves (DPNs) in patients with premature ejaculation is greater than in healthy persons (Chinese Medical Journal, 122: 3017-3019, 2009). Based on these observations, a method called selective resection of DPNs, in which roughly half of the distributed DPNs of a patient with premature ejaculation are selectively resected (International Journal of Andrology, 35: 873-879, 2012), and a method in which CT-guided unilateral cryoablation is performed on DPNs (Journal of Vascular and Interventional Radiology, 24: 214-219, 2013), have been proposed to improve short IELT.
These methods, in which some DPNs are resected can indeed extend IELT. However, because such operations are irreversible, it is impossible to modify IELT after the operation—even if IELT ends up being longer than desired or needs to be shortened.
Further, a method of extending IELT of patients with premature ejaculation using pulsed radiofrequency (PRF) has been proposed (Journal of Andrology, 31: 126-130, 2010 (Basel et al)). PRF was performed on the right and left DPNs with an impedance setting of 200-450 ohms and a radiofrequency generator output setting of 2×20 ms/s and 45 V at 42° C. for 180 sec. As a result, IELT of patients was extended from 18.5±17.9 to 139.9±55.1 sec three weeks after the procedure.
Furthermore, sexual satisfaction scores for the patients and their partners were significantly improved three weeks after the procedure when compared with sexual satisfaction scores before the procedures. Although IELT was not evaluated in a follow-up period after the period of three weeks after the procedure, none of the patients or their partners reported any treatment failure during the follow-up period; the mean follow-up period was 8.3±1.9 months.
The above result indicates that the effect of PRF can be maintained for at least about 8.3 months with a single procedure, leading to speculation that the effect of this procedure may have resulted from a structural change in DPNs.
In Basel et al, it was asserted that PRF neuromodulation has recently been described as an alternative technique to resection of nerves, in which relatively high voltage is applied near nerves without nerve injury. However, citation is made to Pain, 73: 159-163, 1997 (Slappendel et al), which indicates that PRF neuromodulation performed for 90 sec at 67° C. and for 90 sec at 40° C. may cause nerve damage and neuritis as adverse effects.
PRF neuromodulation conditions in Basel were 42° C./180 sec, which includes a higher procedure temperature and longer procedure time than the 40° C./90 sec conditions employed in Slappendel et al. Combining this with the fact that the effect of the procedures in Basel lasted for as long as 8.3 months, it is reasonable to conclude that the effect of extending IELT in the procedure performed in Basel was caused by structural change to the nerves.
As explained above, the procedure of using PRF on DPNs described in Basel is an irreversible operation that causes structural change to DPNs. Thus, similar to nerve resection, IELT is not adjustable after PRF procedures are performed on DPNs.
As such, there is no known procedure for treating premature ejaculation that exerts its effect only when needed, does not result in systemic adverse effects, and does not rely on irreversible operations such as nerve resection or nerve injury, in which nerves cannot recover after the operation is performed.